In a number of applications, a sheet having a plurality of regularly or irregularly spaced pores therein is utilized. For example, such a porous sheet might be utilized as a component in the manufacture of filters, ink jet printer cartridges or fuel injectors. Alternatively, such a porous sheet could be used for generating an aerosol, spray or mist that could be used in the delivery of pharmaceutically active drugs or diagnostic agents.
The pharmaceutically active drug or diagnostic agent could be delivered in a variety of different ways, including but not limited to nasal, oral, topical, dermal, vaginal, intra-tracheal instillation, or ocular. In the preferred embodiment of this invention, a pharmaceutically active drug or diagnostic agent can be delivered inside the human body through the inhalation of an aerosol, spray or mist of said drug or agent generated using an intrapulmonary delivery system. One component of this intrapulmonary delivery system is the sheet containing a plurality of pores. For the purposes of liquid formulations, the aerosol is produced by energizing the liquid formulation, causing the liquid formulation to pass through the sheet containing a plurality of nozzle pores (the array). The attributes of this porous sheet will facilitate the desired control over the particle size distribution (PSD) and emitted dose (ED) of the aerosol treated for inhalation into a subject's lungs. Some existing intrapulmonary delivery devices also provide mechanisms to control the amount of drug delivered to the patient. Examples of the existing intrapulmonary drug delivery devices include Metered Dose Inhalers (MDIs), Dry Powder Inhalers (DPIs) and Nebulizers.
Intrapulmonary delivery of pharmaceutically active drugs or diagnostic agents to the respiratory tract generally requires that the aerosolized particles have a diameter of 12 microns or less. Depending on the intended usage; topical or systemic, the optimal range of particle size distribution can vary. Thus, for topical applications the generally accepted range for an aerosolized particle is in the range of 1.0 to 12.0 microns, preferably 2 to 6 microns. For systemic delivery applications, this range in generally in the 0.25 to 6.0 micron range, preferably 0.5-4 microns, more preferably 1-3.5 microns.
U.S. Pat. Nos. 5,544,646; 5,709,202; 5,497,763; 5,7182,222; 5,660,166; 5,823,178; 5,829,435; 5,906,202, 5,497,944; 5,758,637; and 3,812,854 describe devices and methods useful in the generation of aerosols suitable for drug delivery. These devices generate fine, uniform aerosols by passing a formulation through a porous sheet that can be created, for example, by laser ablation. Examples of available devices that use similar methods of aerosol generation include but are not limited the Pari E-flow®, Aerogen Aeroneb®, Omron Micro-air®, Boehringer-Ingelheim Respimat®, the Medspray® aerosol device, and the Aradigm AERx® system.
In the systems and methods cited above, the emitted dose of the liquid formulation or measure of aerosolization efficiency is affected by a number of variables including the characteristics of the porous sheet. Utilizing embodiments of this invention facilitates an additional degree of control over the efficiency of aerosol generation and drug delivery.
Previously, the advantages of having all pore sizes the same has been stressed. For example, in U.S. Pat. No. 3,812,854, “in the preferred embodiment of this invention, wherein aerosols for inhalation therapy are produced, it is most often preferred to have uniform particle sizes. Bodies having uniform pore diameters in the range of from 0.5 to 5 microns produce aerosols ideal for many inhalation applications.”
Controlling the aerosolization efficiency, or amount of formulation emitted through the characteristics deliberately introduced to the porous sheet as described in this invention can potentially improve the utilization and delivery of a pharmaceutically active drug or diagnostic agent to the intended target within the respiratory tract. A modified porous sheet of the invention can potentially lead to a reduction in the cost of the liquid formulation container utilizing this porous sheet and reduce, thereby, the cost of treatment for a patient.